Noninsulin dependent diabetes mellitis (NIDDM) occurs much more commonly among the Gila River Indians than in any other population in the world. Among this Indian population, the diabetes occurs more commonly in offspring of a diabetic mother than in an offspring of nondiabetic parents. The reasons for this are unknown. In this study we have planned to determine the inherited metabolic abnormality that predisposes the former group of offspring to develop NIDDM. The protocol is a cross-sectional and longitudinal study of the offspring of the two parental types in the Pima Indian population. Due to the extremely high incidence rate of NIDDM in this population, a sufficient number of offspring of diabetic mothers will develop NIDDM within 5 years such that it will be possible to determine which metabolic parameter, if any, is predictive of NIDDM. We will be studying many aspects of carbohydrate metabolism, both in vivo and in vitro, in the initial cross-sectional comparisons and also in the longitudinal study. To date 85 subjects have been studied in the initial cross-sectional phase of this project. Comparisons of carbohydrate metabolism between the two parental types cannot be made as yet because of insufficient numbers of patients with no diabetic parents. Considerable interesting data has been forthcoming however. It is apparent that increasing obesity is not associated with increasing evidence of a "post-receptor defect" in insulin action in vivo. The maximal oxygen uptake, as an estimate of physical fitness appears to account for about 25% of the variance observed in the insulin-stimulated glucose disposal rate at low or high insulin concentrations. The maximal insulin stimulated glucose transport rate in isolated adipocytes is only weakly correlated with the maximal insulin stimulated glucose disposal rate in vivo.